Pope Francis has urged leaders of the Group of 20 nations to abandon the "futile pursuit" of a military solution in Syria and work instead for dialogue and negotiation to end the conflict.
In a letter to the G20 host, Russian president Vladimir Putin, Francis lamented that "one-sided interests" had prevailed in Syria, preventing a peaceful solution and allowing the continued "senseless massacre" of innocents.
Francis has escalated his call for peace in Syria amid threatened US-led military strikes following a chemical weapons attack.
The pontiff will host a peace vigil in St Peter's Square on Saturday.
On Thursday, the Vatican summoned ambassadors accredited to the Holy See to outline its position, calling for respect for all minorities, including Christians, and that Syria's opposition forces distance themselves from extremists.
Archbishop Dominique Mamberti, the Vatican's foreign minister, noted that the August 21 attack had generated "horror and concern" from around the world.
"Confronted with similar acts one cannot remain silent, and the Holy See hopes that the competent institutions make clear what happened and that those responsible face justice," he told the 71 ambassadors gathered.
The archbishop did not refer explicitly to the threat of military strikes to punish the Syrian regime for the attack. But he said the main priority was to stop the violence which he said risked involving other countries and creating "unforeseeable consequences in various parts of the world".
The Vatican, he said, called for a return to dialogue and for the country to not be split up along ethnic or religious lines.
Minorities, including Christians, must have their basic rights guaranteed, including their right to profess their religion, he said. And he called for the opposition to distance itself from extremists, isolate them "and openly and clearly oppose terrorism" - a reference to the al-Qaida-affiliated rebels fighting against the government.
The Assad family's four-decade iron rule over Syria long has rested on support from the country's ethnic and religious minorities, including Christians, Shia Muslims and Kurds. The Assad family and key regime figures are Alawites, followers of an offshoot of Shia Islam, while most rebels and their supporters are Sunni Muslims.
As a result, the Catholic Church has toed a careful line on Syria, staying largely silent at the start of the civil war even after the regime's brutal crackdown on dissent.
As the violence raged, the Vatican stepped up its call for dialogue. And amid the US threat of military intervention, Vatican and church officials have warned that a world war could erupt, with Christians in the region bearing the brunt of the fallout.